This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A stochastic molecular dynamic model is used to characterize the homeostatic mechanisms and glial geometry in perisynaptic space of a glutamatergic synapse in the accumbens. A three-dimensional model of an archetypal synapse is used in Monte Carlo simulations that include neurotransmitter diffusion, binding to transporters and receptors. The model incorporates random extracellular space geometry to quantify the role of ECS in homeostasis. We use this framework to estimate effective diffusion and provide a more accurate prediction of geometric tortuosity in the perisynaptic region.